Hypofractionated Proton Beam Radiotherapy for Hepatocellular Carcinoma

A Phase II Study Using Hypofractionated Proton Beam Radiotherapy for Hepatocellular Carcinoma

This phase II study is to evaluate the effectiveness of hypofractionated proton beam therapy (PBT) for HCC patients in hepatitis B endemic area.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Proton Beam Therapy

Detailed Description

The primary endpoint is local progression free survival. The trial is a single arm phase II trial with the historical arm. The expected 3-year local progression free survival for patient with HCC patients treated with proton beam therapy would be 80%. With a power of 80% and a type I error level of 10%, evaluable 40 patients are required to reject that the null hypothesis that true 3-year local progression free survival rate is ≤65%. Considering the 10% unevaluable patients due to loss of follow up, a total 45 eligible patients for each arms will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 411-769
      • National Cancer Center, Korea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HCC diagnosed as (i) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level greater than 200 IU/ml and a radiologically compatible feature with HCC in one or more CT/MRI/angiograms, or (ii) the presence of risk factors including hepatitis B or C virus and liver cirrhosis, a serum a-fetoprotein (AFP) level less than 200 IU/ml, and a radiologically compatible feature with HCC in two or more CT/MRI/angiograms or (iii) histological confirmation
• HCC patients who were not prospective suitable or refused for any other treatment, such as surgery or local ablation therapy, or recurrent or residual tumor after other treatments.
• without evidence of extrahepatic metastasis
• All target tumors must be encompassable within single irradiation field (15x15 cm maximum)
• no previous treatment to target tumors by other forms of RT
• liver function of Child-Pugh class A or B7 (Child-Pugh score of ≤7)
• Age of ≥18 years
• performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) score
• WBC count ≥ 2,000/mm3; hemoglobin level ≥ 7.5 g/dL; platelet count ≥ 25,000/mm3; and adequate hepatic function (total bilirubin ≤ 3.0 mg/dL; AST and ALT < 5.0× upper limit of normal; no ascites)
• no serious comorbidities other than liver cirrhosis
• written informed consent

Exclusion Criteria:

• evidence of extrahepatic metastasis
• age < 18 years
• liver function of Child-Pugh class B8-9 and C (Child-Pugh score of >7)
• previous history of other forms of RT adjacent to target tumors
• poor performance status of 3 to 4 on the Eastern Cooperative Oncology Group (ECOG) score
• multicentric HCCs, except for those with the following two conditions: *multinodular aggregating HCC that could be encompassed by single clinical target volume and within single irradiation field (15x15 cm maximum) *lesions other than targeted tumor that were judged as controlled with prior surgery and/or local ablation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Proton Beam Therapy; Prescription dose to PTV as according to the following dose escalation schema: Arml 1: 60 GyE /10 fx, 6GyE fraction dose, 5 days/week, for HCC free from the alimentary tract (i.e., stomach, duodenum, esophagus, small and large bowel) (more than 2cm from clinical target volume), TLV30 <40%, and/or RLV30 <30%) Arm 2: 50 GyE /10 fx, 5GyE fraction dose, 5 days/week, for HCC close to the alimentary tract (less than 2cm from clinical target volume) but not contact with the alimentary tract, TLV30<50% and RLV30<40% Arm 3: 35 GyE /10 fx, 4GyE fraction dose, 5 days/week, for HCC contact to the alimentary tract (contact with clinical target volume), TLV30<60%, and/or RLV30<50%; Dose prescription : 95% isodose volume of prescribed dose encompassed PTV

Radiation: Proton Beam Therapy; - Prescription dose to PTV as according to the following dose escalation schema: Arml 1: 60 GyE /10 fx, 6GyE fraction dose, 5 days/week, for HCC free from the alimentary tract (i.e., stomach, duodenum, esophagus, small and large bowel) (more than 2cm from clinical target volume), TLV30 <40%, and/or RLV30 <30%) Arm 2: 50 GyE /10 fx, 5GyE fraction dose, 5 days/week, for HCC close to the alimentary tract (less than 2cm from clinical target volume) but not contact with the alimentary tract, TLV30<50% and RLV30<40% Arm 3: 35 GyE /10 fx, 4GyE fraction dose, 5 days/week, for HCC contact to the alimentary tract (contact with clinical target volume), TLV30<60%, and/or RLV30<50% - Dose prescription : 95% isodose volume of prescribed dose encompassed PTV; Other Names: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
local progression-free survival	To evaluate the local progression-free survival (LPFS) in HCC patients treated with hypofractionated proton beam radiotherapy.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	To evaluate compliance of proton beam radiotherapy for HCC by analyzing acute and late treatment-related toxicity, such as radiation-induced hepatic toxicity and gastrointestinal tract toxicity; To evaluate the impact of hypofractionated proton beam radiotherapy for HCC by analyzing the tumor response rate, local disease-free survival (DFS) and overall survival (OS) rate	Up to 2years until study closed

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Tae Hyun Kim, Ph.D, National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start: June 7, 2012
• Primary Completion (Actual): April 30, 2017
• Study Completion (Actual): April 30, 2017

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 16, 2012
• First Posted (Estimate): July 18, 2012

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: NCCCTS-12-622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided